Skin tumors can be effectively induced in mice by the repetitive application of a carcinogen. The relative order of sensitivity to complete carcinogenesis is Sencar > CD-1 > C57BL/6 ≥ BALB/c ≥ ICR/Ha Swiss > C3H. Skin tumors in mice can also be induced by the sequential application of a sub-threshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a weak or noncarcinogenic tumor promoter (promotion phase). The relative order of sensitivity to ...

The mouse skin carcinogenesis protocol is a unique model for understanding the molecular events leading to oncogenic transformation. Mutations in the Ha-ras gene, and the presence of functional cyclin D1 and the EGF receptor, have proven to be important in this system. However, the signal transduction pathways connecting these elements during mouse skin carcinogenesis are poorly understood. This paper studies the relevance of the Akt and ERK pathways in the different stages of chemically ...

Binding of [20-3H]phorbol 12,13-dibutyrate ([3H]PDB) to intact human promyelocytic leukemia cells susceptible (HL-60) or resistant (R-35) to phorbol ester-induced differentiation was characterized. Specific binding of [3H]PDB to both HL-60 and R-35 cells at 37 degrees C reached a maximum within 15-20 min. Maximal specific [3H]PDB binding to HL-60 cells was followed by a decline (down regulation) of radioactivity. This down regulation was temperature dependent, because no loss of ...

Rel/NF-kappaB transcription factors are implicated in the control of cell proliferation, apoptosis and transformation. The key to NF-kappaB regulation is the inhibitory IkappaB proteins. During response to diverse stimuli, IkappaBs are rapidly phosphorylated by IkappaB kinases (IKKs), ubiquitinated and undergo degradation. We have investigated the expression and function of NF-kappaB, IkappaB inhibitors and IKKs in normal prostate epithelial cells and prostate carcinoma (PC) cell lines ...

In this study, the effects of combining ursolic acid + resveratrol, for possible combined inhibitory effects on skin tumor promotion, were evaluated. Ursolic acid, resveratrol, and the combination of ursolic acid + resveratrol were applied topically prior to 12-O-tetracanoylphorbol-13-acetate (TPA) treatment on mouse skin to examine their effect on TPA-induced signaling pathways, epidermal hyperproliferation, skin inflammation, inflammatory gene expression, and skin tumor promotion. The ...

The effects of nonpromoting and weakly promoting diterpenes on skin tumor promotion by 12-O-tetradecanoylphorbol 13-acetate (TPA) were investigated. When phorbol and phorbol 12,13-diacetate (both nonpromoting) were given simultaneously with TPA after 7,12-dimethylbenz[a]-anthracene (DMBA) initiation in female mice, they had no effect on TPA promotion. However, the nonpromoter 4-O-methyl-TPA and the weak promoter mezerein were found to inhibit TPA promotion in a dose-dependent manner when ...

The effects of fluocinolone acetonide (FA), retinoic acid (RA), and tosylphenylalanine chloromethyl ketone (TPCK) on two-stage promotion after 7,12-dimethylbenz[a]-anthracene (DMBA) initiation in female Sencar mice were investigated. The two-stage promotion protocol was achieved by twice weekly applications of 2 microgram of 12-O-tetradecanoylphorbol 13-acetate (TPA) for 2 weeks (stage I) followed by twice weekly applications of mezerein for 18 weeks (stage II). Separately stage I and II ...

Gap junctional intercellular communication (GJIC) of cultured mouse epidermal cells is mediated by a gap junction protein, connexin 43, and is dependent on the calcium concentration in the medium, with higher GJIC in a high-calcium (1.2 mM) medium. In several mouse epidermal cell lines, we found a good correlation between the level of GJIC and that of immunohistochemical staining of E-cadherin, a calcium-dependent cell adhesion molecule, at cell-cell contact areas. The variant cell line ...

2-Methoxyestradiol (2-ME), an endogenous metabolite of 17beta-estradiol, is present in human blood and urine. Here we show for the first time that 2-ME significantly inhibited the growth of normal prostate epithelial cells and androgen-dependent LNCaP and androgen-independent DU145 prostate cancer cells. This growth inhibition was accompanied by a twofold increase in the G(2)/M population, with a concomitant decrease in the G(1) population, as shown by cell-cycle analysis. 2-ME treatment ...

Polyamine levels were evaluated in human HL-60 promyelocytic leukemia cells after treatment with inducers of terminal differentiation. Differentiation in these cells was determined by increases in the percentage of morphologically mature cells and in lysozyme activity. Treatment of the HL-60 cells with phorbol 12-myristate-13-acetate (PMA), phorbol 12,13-didecanoate or other inducers of terminal differentiation such as dimethylsulfoxide and retinoic acid resulted in increased levels of ...

TUMOUR-PROMOTING agents have been defined by their ability to promote tumour formation on carcinogen-initiated mouse skin. The most potent of these agents are the diesters of phorbol which are the active components of croton oil, the classic promoting substance. Phorbol esters can be chemically modified in a number of positions to form molecules with a wide range of promoter potency1. Such modifications have been useful in determining structure-function relationships2. A good correlation ...